UW News

January 28, 2010

Hepatitis C virus reprograms liver cell metabolic functions

Hepatitis C virus is notorious for its ability to stay under the immune system radar and cause chronic and often debilitating liver disease. Now, a multi-disciplinary team of researchers has shown how the virus disrupts the normal metabolic functioning of the liver. This groundbreaking study is the first to use sensitive mass spectrometry and computational methods to analyze changes in the protein and lipid profiles of liver cells during hepatitis C virus infection.

The research team was led by UW virologist Michael G. Katze, professor of microbiology, and included Charles M. Rice of Rockefeller University, New York; and Richard D. Smith of the Pacific Northwest National Laboratory, Richland, Wash.

The findings published in the January PLoS Pathogens reveal that hepatitis C virus exploits the metabolic resources of liver cells to support viral replication. Viruses rely on the cells they infect to provide the energy and building blocks necessary to survive and propagate. This process results in massive disruption of liver cell metabolism.

The researchers analyzed hepatitis C virus-induced changes in the protein and lipid composition of liver cells. They used computational modeling techniques to identify proteins that are central points for connecting and controlling metabolic pathways. This approach led to the identification of mitochondrial fatty acid enzymes as key cellular proteins targeted by the hepatitis C virus.

“These findings are important,” said Katze, “because the same metabolic changes we observed in liver cells were also found in liver biopsy specimens taken from hepatitis C virus-infected liver transplant patients that had rapid recurrence of liver fibrosis. This raises the prospect that these enzymes may be useful as diagnostic indicators or possibly even as drug targets.”

The results were published in the PLoS Pathogens article, “Temporal proteome and lipidome profiles reveal hepatitis C virus-associated reprogramming of hepatocellular metabolism and bioenergetics.”

The study was conducted as part of a National Institute on Drug Abuse federally supported research program to apply leading-edge genomic and proteomic technologies and bioinformatics approaches to study hepatitis C virus-associated liver disease. Hepatitis C virus infection is a major medical consequence of injection drug use. The National Institute on Drug Abuse funding supports the development of new and effective treatment and prevention interventions to alleviate the social, medical, and economic costs associated with Hepatitis C. The National Institute on Drug Abuse is one of the National Institutes of Health.

Acute hepatitis C infection is underreported, according to the Centers for Disease Control and Prevention, because it usually has no or only mild symptoms. The infection becomes chronic in about 75 percent to 85 percent of cases. Chronic infection can last a lifetime and can lead to liver cancer or permanent scarring of the liver, called cirrhosis. In many cases cirrhosis is the first symptom of chronic hepatitis C. The Centers for Disease Control estimates that chronic hepatitis C affects about 3.2 million people in the United States. It is one of the leading reasons for liver transplant surgery.

In addition to Katze, Rice and Smith, the researchers on the study were Deborah L. Diamond, Kathie-Anne Walters, and Sean C. Proll, all from the UW; Andrew J. Syder of Rockefeller University; Jon M. Jacobs, Christina M. Sorenson, Marina A. Gritsenko Qibin Zhang, Rui Zhao, Thomas O. Metz, David G. Camp II, Katrina A. Walters and Jason E. McDermott, all from the Pacific Northwest National Laboratory.

PLoS Pathogens is an open-access, peer-reviewed journal published monthly by the Public Library of Science (PLoS), a nonprofit organization created to make the world’s scientific and medical research literature a freely available public resource.